Arginine deficiency or a deficiency of any urea cycle substrates has been shown to be associated with increased orotic aciduria. Orotic acid excretion represents a valuable metabolite that may be indicative of arginine availability in numerous proteins. This research proposal is designed to determine the influence of amino acid imbalances on arginine availability, urea cycle operation and pyrimidine biosynthesis. Previous studies in our laboratory have shown that any amino acid administered in excess is capable of inducing an ortic aciduria. We plan to evaluate the influence of various amino acids on dietary arginine availability as indicated by in vivo and in vitro synthesis of urea and orotic acid. Each amino acid will be examined in vivo and in vitro for their ability to alter pyrimidine and urea biosynthesis. Both pathways will be examined for enzymatic and substrate alterations induced by the amino acids. The minimum quantity of each amino acid required to alter these two pathways will also be examined. The mechanism by which each amino acid alters pyrimidine biosynthesis will be determined. Orotic acid will be isolated as indices of whether the alteration is occurring in one or the other pathway. Dietary manipulations of individual amino acids will be made in a predetermined fashion so that the potential antagonistic action of the amino acids on urea cycle operation can be observed. Dietary manipulations of intravenous solutions of individual amino acids will be performed in an attempt to elucidate the effects of various amino acids on arginine availability, urea cycle operation and pyrimidine biosynthesis. These studies will add valuable information on the relationship of amino acids to nitrogen detoxification by urea formation and pyrimidine biosynthesis. These data will evaluate the influence of amino acid imbalances on arginine availability. These data will also be of considerable importance in the evaluation of the amino acid content of intravenous solutions used in patients with various disorders.